METABOLIC ASPECTS OF BODY WEIGHT CHANGE IN DEPRESSION

抑郁症中体重变化的代谢方面

• 批准号: 3380362
• 负责人: MADELYN H FERNSTROM
• 金额: $ 11.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3380362
• 关键词: antidepressants; bioenergetics; body temperature; body weight; caloric dietary content; desipramine; drug adverse effect; human subject; laboratory rat; major depression; metabolism; nutrition related tag; oximes; oxygen consumption; radioimmunoassay

Antidepressant treatment is reputed to be associated with unwanted, excessive weight gain. Regulation of body weight is a complex problem and can result from increase caloric intake, decreased caloric expenditure, or both. In this proposal, based on preliminary findings, the major focus in primarily on caloric expenditure, however selected studies also address food preference and caloric intake. The working hypothesis is that antidepressant-induced weight gain in humans follow from a reduction in caloric expenditure. The proposed studies will dissect the effects of antidepressant drugs on metabolism and metabolic rate. Studies will be performed in depressed humans and in rats. In depressed inpatients hospitalized for 4 weeks, the effects of two antidepressants (desipramine and fluvoxamine) on metabolic rate will be compared. Data will also be obtained on caloric intake in treated subjects. The results should expose which drug type(s) induce a decline in metabolic rate and/or influence body weight. Studies in depressed outpatients will explore for metabolic changes in subjects treated for 4 or more months with imipramine. These studies will characterize the time-course of metabolic effects, and determine if reductions in metabolic rate observed after 2-4 weeks of treatment are sustained over longer periods. Finally, experiments will be pursued in rats to elucidate the mechanism(s) by which drug- induced changes in metabolism occur. In both humans and rats, the actual experiments involve measurements of metabolic rate by quantitation of oxygen inspiration and carbon dioxide expiration. Measurements in blood of key energy substrates and insulin will also be made, by chemical and radioimmunoassay techniques. These latter determinations will be an important complement to the metabolic rate determinations made using inspired and expired gases. Overall, the results of these studied should help to determine that portion of the depressed population susceptible to antidepressant-induced weight gain, and the pharmacologic and metabolic causes of their increase in body weight. The findings may therefore be useful in formulating a pharmacologic strategy that will avoid weight gain as a side- effect to antidepressant treatment.

抗抑郁治疗被认为与 不必要的过度增重 调节体重是一种 这是一个复杂问题， 减少热量消耗，或两者兼而有之。 在这份提案中，根据 初步调查结果，主要集中在主要是热量 然而，一些研究也涉及粮食问题， 偏好和热量摄入。 工作假设是， 抗抑郁药诱导的体重增加在人类遵循一个 减少卡路里消耗。 拟议的研究将 剖析抗抑郁药物对新陈代谢的影响， 代谢率 研究将在抑郁症患者中进行 在老鼠身上。 住院4周的抑郁症患者， 两种抗抑郁药（地昔帕明和氟伏沙明）对 将比较代谢率。 还将获得以下数据： 治疗受试者的热量摄入。 结果应该会暴露 哪种药物类型诱导代谢率下降和/或 影响体重。 对抑郁症门诊患者的研究将 探索接受4次或以上治疗的受试者的代谢变化 几个月的丙咪嗪。 这些研究将描述 代谢影响的时间过程，并确定是否减少 治疗2 - 4周后观察到的代谢率 持续时间更长。 最后，实验将 在大鼠中进行研究，以阐明药物- 引起代谢的变化。 在人类和老鼠身上， 实际的实验包括测量代谢率 通过定量吸入氧气和二氧化碳 过期 血液中关键能量底物的测量， 还将通过化学和放射免疫测定法制备胰岛素 技术. 后面的这些决定将是重要的 补充代谢率测定， 吸入和呼出的气体。 总的来说，这些研究的结果 应该有助于确定抑郁人群中 易受抗抑郁药诱导的体重增加， 它们在体内增加的药理学和代谢原因 重量. 因此，研究结果可能有助于制定 药理学策略，将避免体重增加作为一个侧面， 对抗抑郁治疗的影响。